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1.
Transfusion ; 61(9): 2658-2667, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34216156

RESUMO

BACKGROUND: The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of severe acute respiratory syndrome coronavirus 2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between multiple serological assays. METHODS: We compared the Ortho, Abbott, Roche, an anti-spike (S) ELISA, and a virus neutralization assay. Relationships relative to FDA-approved cutoffs under the CCP emergency use authorization were identified in convalescent plasma from a cohort of 79 donors from April 2020. RESULTS: Relative to the neutralization assay, the spearman r value of the Ortho Clinical, Abbott, Roche, anti-S ELISA assays was 0.65, 0.59, 0.45, and 0.76, respectively. The best correlative index for establishing high-titer units was 3.87 signal-to-cutoff (S/C) for the Abbott, 13.82 cutoff index for the Roche, 1:1412 for the anti-S ELISA, 1:219 by the neutralization assay, and 15.9 S/C by the Ortho Clinical assay. The overall agreement using derived cutoffs compared to a neutralizing titer of 1:250 was 78.5% for Abbott, 74.7% for Roche, 83.5% for the anti-S ELISA, and 78.5% for Ortho Clinical. DISCUSSION: Assays based on antibodies against the nucleoprotein were positively associated with neutralizing titers and the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/terapia , Teste Sorológico para COVID-19 , Comorbidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunização Passiva , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Soroepidemiológicos , Adulto Jovem , Soroterapia para COVID-19
2.
Clin Chem ; 66(8): 1055-1062, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32402061

RESUMO

BACKGROUND: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid proliferation of serologic assays. However, little is known about their clinical performance. Here, we compared two commercial SARS-CoV-2 IgG assays. METHODS: 103 specimens from 48 patients with PCR-confirmed SARS-CoV-2 infections and 153 control specimens were analyzed using SARS-CoV-2 serologic assays by Abbott and EUROIMMUN (EI). Duration from symptom onset was determined by medical record review. Diagnostic sensitivity, specificity, and concordance were calculated. RESULTS: The Abbott SARS-CoV-2 assay had a diagnostic specificity of 99.4% (95% CI; 96.41-99.98%), and sensitivity of 0.0% (95% CI; 0.00-26.47%) at <3 days post symptom onset, 30.0% (95% CI; 11.89-54.28) at 3-7d, 47.8% (95% CI; 26.82-69.41) at 8-13d and 93.8% (95% CI; 82.80-98.69) at ≥14d. Diagnostic specificity on the EI assay was 94.8% (95% CI; 89.96-97.72) if borderline results were considered positive and 96.7% (95% CI; 92.54-98.93) if borderline results were considered negative. The diagnostic sensitivity was 0.0% (95% CI; 0.00-26.47%) at <3d, 25.0% (95% CI; 8.66-49.10) at 3-7d, 56.5% (95% CI; 34.49-76.81) at 3-7d and 85.4% (95% CI; 72.24-93.93) at ≥14d if borderline results were considered positive. The qualitative concordance between the assays was 0.83 (95% CI; 0.75-0.91). CONCLUSION: The Abbott SARS-CoV-2 assay had fewer false positive and false negative results than the EI assay. However, diagnostic sensitivity was poor in both assays during the first 14 days of symptoms.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Anticorpos Antivirais/imunologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/virologia , Reações Falso-Positivas , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Pandemias , Pneumonia Viral/virologia , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , SARS-CoV-2 , Sensibilidade e Especificidade , Fatores de Tempo
3.
Ann Hematol ; 96(10): 1667-1672, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28762079

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, syndrome of excessive and ineffective activation of the immune system. The majority of the reported data on HLH is from pediatric patients and lacks specificity. This makes HLH diagnosis challenging especially in adults where HLH is triggered by many conditions and can resemble many disease entities. Elevated ferritin is one of the diagnostic criteria for HLH. We determined the conditions associated with elevated ferritin at our medical center to assess how specific ferritin is for predicting HLH. We retrospectively reviewed all ferritin results >10,000 µg/L in pediatric and adult patients. The most common condition associated with elevated ferritin was hematologic malignancy in adults (25.7%) and HLH in pediatric patients (48.9%). HLH was diagnosed in 14.2% of adults and 48.9% of children with ferritin >10,000 µg/L. Hyperferritinemia occurs in a variety of conditions and is not specific for adult or pediatric HLH. Common causes of elevated ferritin should be considered before entertaining the possibility of HLH, especially in adult patients.


Assuntos
Ferritinas/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Clin Chem ; 62(2): 360-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26546635

RESUMO

BACKGROUND: Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. METHODS: To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3-month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. RESULTS: Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short-term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs-cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. CONCLUSIONS: The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients.


Assuntos
Biomarcadores/sangue , Galectina 3/sangue , Insuficiência Cardíaca/sangue , Adulto , Idoso , Proteínas Sanguíneas , Feminino , Galectinas , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Valores de Referência , Troponina I/sangue
6.
J Appl Lab Med ; 8(4): 689-699, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37186660

RESUMO

BACKGROUND: The Freelite assay (The Binding Site) is utilized to quantify serum immunoglobulin free light chains (sFLC), which is crucial for diagnosing and monitoring plasma cell dyscrasias (PCDs). Using the Freelite test, we compared methods and evaluated workflow differences across two analyzer platforms. METHODS: sFLC concentrations were measured in 306 fresh serum specimens (cohort A) and 48 frozen specimens with documented sFLC >20 mg/dL (cohort B). Specimens were analyzed on the Roche cobas 8000 and Optilite analyzers using the Freelite κ and λ assays. Performance was compared using Deming regression. Workflow was compared by assessing turnaround time (TAT) and reagent usage. RESULTS: For cohort A specimens, Deming regression revealed a slope of 1.04 (95% CI, 0.88-1.02) and an intercept of -0.77 (95% CI, -0.57 to 1.85) for sFLCκ and a slope of 0.90 (95% CI, -0.04 to 1.83) and intercept of 1.59 (95% CI, -3.12 to 6.25) for sFLCλ. Regression of the κ/λ ratio revealed a slope of 2.44 (95% CI, 1.47-3.41) and intercept of -8.13 (95% CI, -16.82 to 0.58) with a concordance kappa of 0.80 (95% CI, 0.69-0.92). The proportion of specimens with TAT >60 min was 0.33% and 8% for the Optilite and cobas, respectively (P < 0.001). The Optilite required 49 (P < 0.001) and 12 (P = 0.016) fewer tests for sFLCκ and sFLCλ relative to the cobas. Cohort B specimens showed similar but more dramatic results. CONCLUSIONS: Analytical performance of the Freelite assays was comparable on the Optilite and cobas 8000 analyzers. In our study, the Optilite required less reagent, had a slightly reduced TAT, and eliminated manual dilutions for samples with sFLC concentrations >20 mg/dL.


Assuntos
Cadeias Leves de Imunoglobulina , Paraproteinemias , Humanos , Fluxo de Trabalho , Paraproteinemias/diagnóstico
7.
Clin Biochem ; 117: 16-22, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34990593

RESUMO

INTRODUCTION: Dried blood spot (DBS) sampling is a minimally invasive method for specimen collection with potential multifaceted uses, particularly for serosurveillance of previous SARS-CoV-2 infection. In this study, we assessed DBS as a potential specimen type for assessing IgG and total (including IgG and IgM) antibodies to SARS-CoV-2 in vaccinated and naturally infected patients. METHODS: Six candidate buffers were assessed for eluting blood from DBS cards. The study utilized one hundred and five paired plasma specimens and DBS specimens from prospectively collected SARS-CoV-2 vaccinated individuals, remnants from those with PCR confirmed SARS-CoV-2 infections, or remnants from those without history of infection or vaccination. All specimens were tested with the Siemens SARS-CoV-2 total assay (COV2T) or IgG assay (sCOVG). RESULTS: The lowest backgrounds were observed with water and PBS, and water was used for elution. Relative to plasma samples, DBS samples had a positive percent agreement (PPA) of 94.4% (95% CI: 94.9-100%) for COV2T and 79.2 (68.4-87.0) for sCOVG using the manufacturer's cutoff. The NPA was 100 % (87.1-100.0 and 85.13-100) for both assays. Dilution studies revealed 100% (95% CI: 90.8-100%) qualitative agreement between specimen types on the COV2T assay and 98.0% (88.0-99.9%) with the sCOVG using study defined cutoffs. CONCLUSION: DBS specimens demonstrated high PPA and NPA relative to plasma for SARS-CoV-2 serological testing. Our data support feasibility of DBS sampling for SARS-CoV-2 serological testing.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Teste para COVID-19 , Manejo de Espécimes/métodos , Anticorpos Antivirais , Imunoglobulina M , Imunoglobulina G , Teste em Amostras de Sangue Seco
8.
J Appl Lab Med ; 8(5): 871-886, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37478837

RESUMO

BACKGROUND: SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection. METHODS: Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing. RESULTS: There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP. CONCLUSIONS: Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Atenção à Saúde , Imunoglobulina G
9.
J Appl Lab Med ; 7(4): 827-833, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35296885

RESUMO

BACKGROUND: Serological assays for SARS-CoV-2 are important tools for diagnosis in patients with negative RT-PCR testing, pediatric patients with multisystem inflammatory syndrome, and serosurveillance studies. However, lateral flow-based serological assays have previously demonstrated poor analytical and clinical performance, limiting their utility. METHODS: We assessed the ADEXUSDx COVID-19 lateral flow assay for agreement with diagnostic RT-PCR testing using 120 specimens from RT-PCR-positive patients, 77 specimens from symptomatic RT-PCR-negative patients, and 47 specimens obtained prepandemic. Specimens collected <14 days from symptom onset in RT-PCR-positive patients were compared relative to the Abbott SARS-CoV-2 IgG assay. RESULTS: The ADEXUSDx COVID-19 Test yielded an overall positive percent agreement (PPA) of 92.5% (95%CI 85.8 to 96.3) and negative percent agreement of 99.2% (95% CI 94.9-100.0) relative to RT-PCR and in prepandemic specimens. Relative to days from symptom onset, the PPA after 13 days was 100% (95% CI 94.2-100); from 7 to 13 days, 89.7 (95% CI 71.5-97.2); and from 0 to 7 days, 53.8 (95% CI 26.1-79.6). The overall agreement between the Abbott and ADEXUSDx assays was 80.9%. Twenty-five specimens were positive by both assays, 9 specimens were negative by both assays, and 8 specimens were positive by only the ADEXUSDx assay. CONCLUSIONS: We demonstrate high PPA and negative percent agreement of the ADEXUSDx COVID-19 assay and diagnostic testing by RT-PCR, with PPA approximately 90% by 7 days following symptom onset. The use of waived testing for antibodies to SARS-CoV-2 with high sensitivity and specificity provide a further tool for combatting the COVID-19 pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/complicações , COVID-19/diagnóstico , Criança , Humanos , Pandemias , SARS-CoV-2/genética , Sensibilidade e Especificidade , Síndrome de Resposta Inflamatória Sistêmica
10.
Hum Immunol ; 83(12): 803-807, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36109290

RESUMO

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham's distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/genética , SARS-CoV-2 , Genótipo , Hospitalização , Antígenos HLA-B/genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-36483341

RESUMO

In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection.

12.
Nat Commun ; 13(1): 882, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169146

RESUMO

SARS-CoV-2 triggers a complex systemic immune response in circulating blood mononuclear cells. The relationship between immune cell activation of the peripheral compartment and survival in critical COVID-19 remains to be established. Here we use single-cell RNA sequencing and Cellular Indexing of Transcriptomes and Epitomes by sequence mapping to elucidate cell type specific transcriptional signatures that associate with and predict survival in critical COVID-19. Patients who survive infection display activation of antibody processing, early activation response, and cell cycle regulation pathways most prominent within B-, T-, and NK-cell subsets. We further leverage cell specific differential gene expression and machine learning to predict mortality using single cell transcriptomes. We identify interferon signaling and antigen presentation pathways within cDC2 cells, CD14 monocytes, and CD16 monocytes as predictors of mortality with 90% accuracy. Finally, we validate our findings in an independent transcriptomics dataset and provide a framework to elucidate mechanisms that promote survival in critically ill COVID-19 patients. Identifying prognostic indicators among critical COVID-19 patients holds tremendous value in risk stratification and clinical management.


Assuntos
COVID-19/imunologia , Imunidade Celular/imunologia , Idoso , Idoso de 80 Anos ou mais , COVID-19/genética , COVID-19/mortalidade , Estado Terminal , Feminino , Expressão Gênica , Humanos , Imunidade Celular/genética , Leucócitos Mononucleares/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , SARS-CoV-2/patogenicidade , Análise de Célula Única , Transcriptoma/imunologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-36310813

RESUMO

Objective: Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population. Design: Single-center cohort study. Setting and participants: Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center. Methods: Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti-SARS-CoV-2 spike antibodies (anti-S) ∼4-7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50-839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL). Results: Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28-88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response. Conclusions: Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.

14.
Respir Care ; 56(4): 412-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21255510

RESUMO

BACKGROUND: Nosocomial pneumonia is a difficult diagnosis to establish in the intensive care unit setting, due to the non-specific nature of the clinical and radiographic findings. Procalcitonin is a circulating biomarker that may become elevated in the presence of bacterial infection. METHODS: We conducted a prospective single-center cohort study at Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital in St Louis, Missouri. In medical and surgical intensive care unit patients with suspected nosocomial pneumonia we measured plasma procalcitonin with an enzyme-linked fluorescent assay. RESULTS: We evaluated 104 consecutive patients with suspected nosocomial pneumonia, 67 (64%) of whom met our predefined clinical and microbiologic criteria for definite nosocomial pneumonia. Though the mean procalcitonin concentration was greater in the 67 patients with definite nosocomial pneumonia (18.3 ± 99.1 ng/mL, median 0.8 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 43.1 ng/mL) than in the 12 patients with definite absence of nosocomial pneumonia (1.7 ± 2.0 ng/mL, median 1.0 ng/mL, 5th percentile 0.0 ng/mL, 95th percentile 6.7 ng/mL), this difference was not statistically significant (P = .66). A procalcitonin cutoff value of > 1 ng/mL yielded a diagnostic sensitivity of 50% and a specificity of 49% for definite nosocomial pneumonia. Receiver operating curve and multivariate logistic regression analyses demonstrated that procalcitonin is inferior to clinical variables for diagnosing nosocomial pneumonia. However, compared to patients with an initial procalcitonin > 1 ng/mL, those with lower procalcitonin had fewer total antibiotic days (13.0 ± 10.3 d vs 19.7 ± 12.0 d, P < .001) and fewer antibiotic days for treatment of nosocomial pneumonia (10.0 ± 5.9 d vs 14.7 ± 7.4 d, P < .001). CONCLUSIONS: Plasma procalcitonin has minimal diagnostic value for nosocomial pneumonia.


Assuntos
Calcitonina/sangue , Infecção Hospitalar/diagnóstico , Unidades de Terapia Intensiva , Pneumonia/diagnóstico , Precursores de Proteínas/sangue , Biomarcadores , Peptídeo Relacionado com Gene de Calcitonina , Infecção Hospitalar/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Missouri/epidemiologia , Pneumonia/epidemiologia , Estudos Prospectivos , Curva ROC , Estatísticas não Paramétricas
15.
HLA ; 98(4): 370-379, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34338446

RESUMO

The experience of individuals with Coronavirus Disease 2019 (COVID-19) ranges from asymptomatic to life threatening multi-organ dysfunction. Specific HLA alleles may affect the predisposition to severe COVID-19 because of their role in presenting viral peptides to launch the adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this population-based case-control study in the midwestern United States, we performed high-resolution HLA typing of 234 cases hospitalized for COVID-19 in the St. Louis metropolitan area and compared their HLA allele frequencies with those of 22,000 matched controls from the National Marrow Donor Program (NMDP). We identified two predisposing alleles, HLA-DRB1*08:02 in the Hispanic group (OR = 9.0, 95% confidence interval: 2.2-37.9; adjusted p = 0.03) and HLA-A*30:02 in younger African Americans with ages below the median (OR = 2.2, 1.4-3.6; adjusted p = 0.01), and several candidate alleles with potential associations with COVID-19 in African American, White, and Hispanic groups. We also detected risk-associated amino acid residues in the peptide binding grooves of some of these alleles, suggesting the presence of functional associations. These findings support the notion that specific HLA alleles may be protective or predisposing factors to COVID-19. Future consortium analysis of pooled cases and controls is warranted to validate and extend these findings, and correlation with viral peptide binding studies will provide additional evidence for the functional association between HLA alleles and COVID-19.


Assuntos
COVID-19 , Antígenos HLA-A , Cadeias HLA-DRB1 , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genética , Humanos , Polimorfismo Genético , SARS-CoV-2
16.
Kidney360 ; 2(6): 996-1001, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35373088

RESUMO

Increased risk of SARS-CoV-2 infection was associated with community prevalence.Increased risk of SARS-CoV-2 infection was associated with exposure to infected family members and personal infection prevention measures.


Assuntos
COVID-19 , COVID-19/epidemiologia , Atenção à Saúde , Humanos , Pacientes Ambulatoriais , Diálise Renal/efeitos adversos , Fatores de Risco , SARS-CoV-2
17.
medRxiv ; 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33791711

RESUMO

The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of SARS-CoV-2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between commercially available serological tests (Ortho, Abbott, Roche), a spike ELISA, and a virus neutralization assay using convalescent plasma from a cohort of 79 donors from April 2020. Relationships relative to FDA-approved cutoffs under the CCP EUA were identified by linear regression and receiver operator characteristic curves. Relative to the Ortho VITROS assay, the r2 of the Abbott, Roche, the anti-Spike ELISA and the neutralizing assay were 0.58, 0.5, 0.82, and 0.44, respectively. The best correlative index for establishing high-titer units was 3.82 S/C for the Abbott, 10.89 COI for the Roche, 1:1,202 for the anti-Spike ELISA, and 1:200 by the neutralization assay. The overall agreement using derived cutoffs compared to the CCP EUA Ortho VITROS cutoff of 9.5 was 92.4% for Abbott, 84.8% for Roche, 87.3% for the anti-S ELISA and 78.5% for the neutralization assay. Assays based on antibodies against the nucleoprotein (Roche, Abbott) and neutralizing antibody tests were positively associated with the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.

18.
Diagn Microbiol Infect Dis ; 99(4): 115300, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388575

RESUMO

The clinical and public health utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing requires a better understanding of the dynamics of the humoral response to infection. To track seroconversion of IgG and IgM antibodies in patients with SARS-CoV-2 infection and its association with patient and clinical factors and outcomes. Residual patient specimens were analyzed on the Abbott ARCHITECT i2000 instrument using the Abbott SARS-CoV-2 IgG assay and prototype SARS-CoV-2 IgM assay. Age, sex, comorbidities, symptom onset date, mortality, and specimen collection date were obtained from electronic medical records. Three hundred fifty-nine longitudinal samples were collected from 89 hospitalized patients 0 to 82 days postsymptom onset. Of all, 51.7% of the patients developed IgG and IgM antibodies simultaneously; 32.8% seroconverted for IgM before IgG. On average, patients seroconverted for IgG by 8 days and for IgM by 7 days postsymptom onset. All patients achieved IgG seropositivity by 19 days and IgM seropositivity by 17 days. Median time to IgG and IgM seroconversion was prolonged and initial levels of IgG were lower in immunocompromised patients and patients <65 years of age compared to immune competent patients and those ≥65 years of age. Immunocompromised patients also had persistently lower levels of IgM that peaked on day 17.6 and decreased thereafter compared to immune competent patients. IgM seroconversion in patients who died reached significantly higher levels later after symptom onset than in those who recovered. SARS-CoV-2 infected patients have similar time to seroconversion for IgG and IgM. However, differences in immune status and age alter time to seroconversion. These results may help guide serologic testing application in COVID-19 management.


Assuntos
Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Soroconversão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , Teste Sorológico para COVID-19/métodos , Feminino , Hospitalização , Humanos , Imunidade Humoral/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Estados Unidos , Adulto Jovem
19.
Clin Biochem ; 41(6): 432-5, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18178161

RESUMO

OBJECTIVES: To determine the feasibility of laboratories to use an instrument's Hemolytic Index (HI) to determine if a test result would be accurate in the presence of hemoglobin-based oxygen carrier HBOC-201. DESIGN AND METHODS: HI values from the Roche Hitachi Modular P800 for samples containing HBOC-201 were determined. HI limits for 24 tests determined by addition of RBC lysate hemoglobin to serum and the instrument manufacturer's HI limits were compared to HI limits for reporting the same tests determined by adding HBOC-201 to plasma. RESULTS: There is a linear relationship (R(2)=0.99) between the HI value on the Modular P800 and HBOC-201 concentrations. Twenty-one of 24 HI limits for reporting results as determined by the manufacturer or adding RBC lysate to serum were more conservative or equal to the limit determined by HBOC-201 interference testing. HBOC-201 interference testing was more conservative for albumin, creatinine, and uric acid. CONCLUSION: For most analytes, the Modular P800 HI provides an accurate, conservative and automated method to determine whether laboratory results should be reported or suppressed when samples contain HBOC-201.


Assuntos
Análise Química do Sangue/instrumentação , Substitutos Sanguíneos/metabolismo , Hemoglobinas/metabolismo , Hemólise , Análise Química do Sangue/métodos , Humanos
20.
Clin Chim Acta ; 384(1-2): 48-51, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17588555

RESUMO

BACKGROUND: Therapeutic drug monitoring for tacrolimus is important for organ transplant patients receiving this immunosuppressant. Current available assays for tacrolimus require sample pre-treatment and operate in a batch mode. Here a no-pretreatment tacrolimus assay, performed on the Dade Behring Dimension analyzer is compared to the Abbott IMx tacrolimus assay and to an LC/MS/MS method. METHODS: Whole blood samples from 2 medical centers and different transplant types (kidney n=103, liver n=81, heart n=27, pancreas n=16, bone marrow n=9, [corrected] lung n=7), were obtained and tacrolimus quantified by each of the 3 assays. RESULTS: The lower limit of the linear range was 1.2 ng/ml on the Dimension assay. Total imprecision was 9.8% and within-run imprecision was 9.6% at a tacrolimus concentration of 3.4 ng/dL. Passing-Bablock regression analysis determined the following relationships: DIMN=(1.16) LC/MS - 0.43, r=0.90 and DIMN=(0.99)IMx - 0.35, r=0.87. CONCLUSIONS: The Dade Behring Dimension [corrected] Tacrolimus assay has adequate imprecision and correlates well with the reference method of LC/MS/MS. The assay appears suitable for clinical use, and has the advantages of not requiring a pretreatment step and the ability to be performed in a random-access mode.


Assuntos
Imunoensaio/instrumentação , Imunoensaio/métodos , Imunossupressores/sangue , Tacrolimo/sangue , Cromatografia Líquida , Humanos , Espectrometria de Massas , Transplante de Órgãos
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